Histoplasmosis is an important respiratory disease and there is a need for a safe and effective vaccine for certain high risk individuals. The ribosomal and RNA fractions from certain bacteria have been used successfully as vaccines. Similar preparations from Histoplasma capsulatum have not been studied for immunogenicity. We propose: (1) to study the immunogenic properties of ribosomes, and RNA from yeast cells of Histoplasma, and (2) to study the physical and chemical characteristics of these preparations with the hope of developing a safe and effective vaccine. The protection induced by immunization with crude ribosomal and RNA-fractions in mice against lethal challenge with yeast and mycelial cells of Histoplasma will be compared with that obtained by immunization with live yeast cells. For challenge, Histoplasma aerosol will be produced with a Henderson apparatus. If difficulty is encountered in producing infectious aerosol, animals will be challenged intravenously. Survival after challenge as well as the persistence of organisms in the internal organs will be used as the criteria for evaluation. The total ribosomal and RNA preparations will be treated with different enzymes, to tentatively identify the chemical nature of immunogenic material. To isolate the specific immunogens, the various undegraded cytoplasmic and mitochondrial ribosomal components will be separated and characterized. The ribosomal protein and RNA will be extracted from ribosomal subunits. The physical and chemical characteristics of ribosomal subunits, ribosomal protein and RNA will be studied by a variety of techniques including sucrose density gradient centrifugation, ultracentrifugation, and polyacrylamide gel electrophoresis. The immunogenicity of the various components will then be determined. It may be possible to separate the protective and allergenic components of immunity in histoplasmosis, by these procedures.